Funds are requested to purchase a VEVO 770" HIGH-RESOLUTION IMAGING SYSTEM to be shared by the laboratories of 6 NIH-funded faculty. The instrument will also be made available for occasional use by other members of the UT Southwestern faculty. The primary users group includes members of the following departments: Internal Medicine/Cardiology (3), Molecular Biology (1), Pediatrics (1), and Internal Medicine/Division of Translational Research (1). The VisualSonics Vevo 770 imaging system is an advanced ultrasound imaging system specifically designed for small animal (rodent) studies. We have identified a group of NIH-funded investigators from a broad array of disciplines whose research would benefit from this technology. Projects proposed by the current users group include: (1) Calcineurin-mediated Regulation of Cardiac Ca2+ Channel, HDAC Inhibition in Cardiac Hypertrophy and Failure (Hill);(2) Control of Cardiac Gene Expression Through Regulated Transcriptional Coactivators, Transcriptional Control of Cardiac Muscle Development, Genes that Regulate Heart Development, and Genetic Dissection of Cardiogenesis (Olson);(3) Modulating Calcineurin Signaling Pathways in Muscle (Rothermel);(4) FOXO4 Promotes Atherosclerosis (Liu);(5);Genetic Regulation of Cardiac Septation (Garg);(6) Innovative Proteomics Research (Garner). Relevance: The ultrasound imaging equipment currently available at UT Southwestern is designed for human use (with a maximal frequency of 15 MHz) and provides minimal resolution for small animal cardiovascular analysis. The spatial resolution of the VisualSonics Vevo 770 imaging system is markedly enhanced. As a result, availability of this system would greatly expand our capacity for multifactorial analysis of cardiac and vascular structure and function. Further, it would for the first time allow investigators at UT Southwestern to non-invasively image the developing heart in utero and quantify arterial blood flow and plaque burden. These capabilities would greatly enhance our studies of cardiovascular disease and development. In addition, this technology would facilitate the testing of several novel therapeutic strategies. As a result, several NIH-sponsored cardiovascular research projects would be vastly enhanced by this important technology. PUBLIC HEALTH RELEVANCE: The heart is a terminally differentiated yet remarkably plastic organ. Disease-related stresses, such as unremitting hypertension or myocardial injury, trigger hypertrophic growth that increases the risk of functional decompensation and malignant rhythm disturbance. Our understanding of mechanisms governing these remodeling reactions is incomplete, and deciphering them may yield insights into the pathogenesis of heart failure, a major source of morbidity and mortality worldwide. Urgency is highlighted by the fact that heart failure is the most important cardiovascular disorder in the Western world from the perspectives of health care resource utilization.